The overall goal of the proposed project is to characterize the molecular role of fatty acid synthase (FAS) in the regulation of neuronal energy metabolism and appetite control. It was previously understood that FAS was present in the brain, but only in non-neuronal cells. However, our results demonstrate that FAS is present, and is active in particular neuronal populations. The role of FAS in these neurons is not understood. Recent studies performed by this group demonstrated that FAS plays a critical role in the regulation of appetite and energy metabolism in mice. Interestingly, FAS appears to play a fundamentally different role in the brain than it does in other tissues. In liver, FAS levels are greatly affected by diet where as brain FAS levels are not. We therefore propose that FAS plays a role in the CNS in regulating appetite, and that this function differs from that in lipogenic tissue. This project has three specific aims. Aim 1 will determine the neuronal localization pattern of FAS relative to known key regulators of feeding. Aim 2 will determine the effect of FAS inhibitors on potential downstream effectors in the hypothalamus. Aim 3 will investigate the role of FAS in neuronal energy metabolism in vitro using a neuronal cell culture system.